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Venetoclax in Combination With Decitabine in r/r AML

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03404193
Recruitment Status : Recruiting
First Posted : January 19, 2018
Last Update Posted : December 12, 2019
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

The goal of this clinical research study is to learn if venetoclax in combination with decitabine can help to control acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (HR-MDS) in newly diagnosed elderly patients or in patients with disease that has relapsed (come back after treatment). The safety of this drug combination will also be studied.

This is an investigational study. Venetoclax and decitabine are FDA approved and commercially available. Venetoclax is FDA approved and commercially available for the treatment of chronic lymphocytic leukemia. Decitabine is FDA approved and commercially available for the treatment of MDS. It is considered investigational to use venetoclax in combination with decitabine to treat AML or HR-MDS.

The study doctor can explain how the study drugs are designed to work.

Up to 280 participants will be enrolled in this study. All will take part at MD Anderson.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome Blasts 10 Percent or More of Bone Marrow Nucleated Cells Blasts 10-20 Percent of Bone Marrow Nucleated Cells Chronic Myelomonocytic Leukemia High Risk Chronic Myelomonocytic Leukemia High Risk Myelodysplastic Syndrome Myelodysplastic Syndrome Recurrent Acute Biphenotypic Leukemia Recurrent Acute Myeloid Leukemia Recurrent Chronic Myelomonocytic Leukemia Recurrent High Risk Myelodysplastic Syndrome Recurrent Mixed Phenotype Acute Leukemia Refractory Acute Myeloid Leukemia Refractory Chronic Myelomonocytic Leukemia Refractory High Risk Myelodysplastic Syndrome Refractory Mixed Phenotype Acute Leukemia TP53 Gene Deletion TP53 Gene Mutation Drug: Decitabine Other: Laboratory Biomarker Analysis Drug: Venetoclax Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 280 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Venetoclax in Combination With 10-Day Decitabine in Newly Diagnosed Elderly or Relapsed/Refractory Acute Myeloid Leukemia and Relapsed High-Risk Myelodysplastic Syndrome
Actual Study Start Date : January 16, 2018
Estimated Primary Completion Date : December 30, 2020
Estimated Study Completion Date : December 30, 2021

Arm Intervention/treatment
Experimental: Treatment (decitabine, venetoclax)
Participants receive decitabine by vein over 1 hour on days 1-10 and may also receive decitabine on days 1-5 after achieving complete remission/complete remission with incomplete count recovery during consolidation/maintenance. Participants also receive venetoclax PO daily on days 1-28 of cycle 1 and on days 1-21 of subsequent cycles. Treatment repeat every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity.
Drug: Decitabine
20 mg/m2 by vein over approximately 1 hour daily x 10 days on days 1-10 of each treatment cycle.
Other Names:
  • 5-Aza-2'-deoxycytidine
  • Aza-TdC
  • Dacogen
  • Decitabine for Injection
  • Deoxyazacytidine
  • Dezocitidine

Other: Laboratory Biomarker Analysis
Correlative studies

Drug: Venetoclax
400 mg by mouth on Days 1-28 of the first cycle and Days 1-21 of all other cycles.
Other Names:
  • ABT-0199
  • ABT-199
  • ABT199
  • GDC-0199
  • RG7601
  • Venclexta

Primary Outcome Measures :
  1. Overall response rate (ORR) of venetoclax in combination with 10-day decitabine [ Time Frame: 3 months ]
    ORR defined as the proportion of patients who had CR (complete remission), CRp (complete remission with incomplete platelet recovery), CRi (complete remission with incomplete count recovery), PR (partial response) or marrow clearance of blasts within 3 months of treatment initiation among adult patients with AML; and complete remission (CR), partial remission (PR) or marrow CR† (mCR) lasting at least 4 weeks for patients with MDS.

Secondary Outcome Measures :
  1. Duration of Response of patients with refractory/relapsed AML treated with this combination. [ Time Frame: 1 year ]
  2. Disease-Free Survival (DFS) of patients with refractory/relapsed AML treated with this combination. [ Time Frame: 1 year ]
  3. Overall Survival (OS) of patients with refractory/relapsed AML treated with this combination. [ Time Frame: 1 year ]
  4. Determination of the number of patients who achieve a hematologic improvement (HI) in platelets, hemoglobin, or absolute neutrophil count (ANC) and the number of patients who achieve > 50% reduction in blasts on therapy with venetoclax/10-day decitabine. [ Time Frame: 1 year ]
  5. Safety of venetoclax in combination with 10-day decitabine in patients with refractory/ relapsed AML. [ Time Frame: Baseline up to 30 days after last dose of study drug ]
    The overall incidence and severity of all reported adverse events using Common Toxicity Criteria v 4.0.

  6. Determination of the number of patients who transition towards stem cell transplantation upon achieving response with the combination venetoclax/10-day decitabine regimen. [ Time Frame: 3 months ]
    Response assessed based by Modified IWG Response Criteria for MDS (Cheson et al, 2006).

  7. Determine the incidence of infections complications per cycle with the Venetoclax in combination with 10-day Decitabine. [ Time Frame: 1 year ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patients with AML, biphenotypic or bilineage leukemia (including a myeloid component) or mixed phenotype acute leukemia (MPAL) who have failed prior therapy; patients with AML should have failed prior therapy or have relapsed after prior therapy; patients with isolated extramedullary AML are eligible
  • Elderly (> 60 year old) patients with newly diagnosed AML or mixed phenotype acute leukemia (MPAL) not eligible for intensive chemotherapy
  • Patients with newly diagnosed AML with poor risk complex karyotype and/or TP53 deletions/mutations equal or younger than 60 year old
  • AML patients with prior history of MDS or CMML who received any therapy or no therapy for the MDS or CMML and progressed to AML, are eligible at the time of diagnosis of AML regardless of any prior therapy for MDS; the World Health Organization (WHO) classification will be used for AML
  • Patients with high-risk MDS with bone marrow blasts between 10% and 20%, relapsed or refractory to prior hypomethylating agent (HMA) therapy, defined as prior receipt of 4 cycles of HMA therapy with failure to attain a response, or relapse after prior response to HMA therapy; patients with high risk chronic myelomonocytic leukemia (CMML) with bone marrow blasts >= 10% regardless of prior therapy
  • Age>/=18 years old
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 3
  • White blood cell count =< 10,000
  • Adequate renal function including creatinine < 2 unless related to the disease
  • Adequate hepatic function including total bilirubin < 2 x upper limit of normal (ULN) unless increase is due to Gilbert's disease or leukemic involvement
  • Provision of written informed consent
  • Oral hydroxyurea and/or one dose of cytarabine (up to 2 g/m^2) for patients with rapidly proliferative disease is allowed before the start of study therapy and while the patient is on active study treatment through cycle 1, as needed, for clinical benefit and after discussion with the principal investigator (PI); concurrent therapy for central nervous system (CNS) prophylaxis or continuation of therapy for controlled CNS disease is permitted
  • Females must be surgically or biologically sterile or postmenopausal (amenorrheic for at least 12 months) or if of childbearing potential, must have a negative serum or urine pregnancy test within 72 hours before the start of the treatment
  • Women of childbearing potential must agree to use an adequate method of contraception during the study and until 3 months after the last treatment; males must be surgically or biologically sterile or agree to use an adequate method of contraception during the study until 3 months after the last treatment

Exclusion Criteria:

  • Patients having received any prior BCL2 inhibitor therapy
  • Patients with t(15;17) karyotypic abnormality or acute promyelocytic leukemia (French-American-British [FAB] class M3-AML)
  • Patients with symptomatic CNS leukemia or patients with poorly controlled CNS leukemia
  • Active and uncontrolled comorbidities including active uncontrolled infection, uncontrolled hypertension despite adequate medical therapy, active and uncontrolled congestive heart failure New York Heart Association (NYHA) class III/IV, clinically significant and uncontrolled arrhythmia as judged by the treating physician
  • Patients with known infection with human immunodeficiency virus (HIV) or active hepatitis B or C
  • Any other medical, psychological, or social condition that may interfere with study participation or compliance, or compromise patient safety in the opinion of the investigator
  • Pregnant or breastfeeding

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03404193

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Contact: Marina Konopleva, MD, PHD 713-794-1628

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United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Marina Konopleva    713-794-1628      
Principal Investigator: Marina Konopleva         
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
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Principal Investigator: Marina Konopleva M.D. Anderson Cancer Center

Additional Information:
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Responsible Party: M.D. Anderson Cancer Center Identifier: NCT03404193    
Other Study ID Numbers: 2017-0912
NCI-2018-00752 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2017-0912 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
First Posted: January 19, 2018    Key Record Dates
Last Update Posted: December 12, 2019
Last Verified: December 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by M.D. Anderson Cancer Center:
Other diseases of blood and blood-forming organs
Acute Myeloid Leukemia
Myelodysplastic Syndrome
Additional relevant MeSH terms:
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Leukemia, Myeloid
Leukemia, Myeloid, Acute
Leukemia, Myelomonocytic, Acute
Leukemia, Myelomonocytic, Chronic
Leukemia, Myelomonocytic, Juvenile
Leukemia, Biphenotypic, Acute
Myelodysplastic Syndromes
Acute Disease
Pathologic Processes
Neoplasms by Histologic Type
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Myelodysplastic-Myeloproliferative Diseases
Disease Attributes
Leukemia, Lymphoid
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action